Posted by West on August 15, 2008, at 12:35:29
In reply to D-amp M-amp MDMA toxicity » cumulative, posted by Dade on August 13, 2008, at 18:56:29
>>Thou studies have often shown high doses of amphetamines cause notorious shaking and loss of balance, low doses (10-15mgs) D-amp improve steadiness and balance, alertness, attention, hand eye coordination, especially in fatigued persons. long distance truckers call amphetamines "co-pilots".
Which studies? How is that relevant?
> > It is my opinion that the changes in dopamine transporters in that study reflect plastic changes, not neurotoxicity.
Your opinion appears to contradict current clinical evidence.
>>Homeostatic changes in the dopamine transporter (and many other systems -- some of which seem to sensitize) are well-known to occur with dopaminergic psychostimulants, and that study does not show anything different.
Which dopaminergic psychostimulants other than the amphetamines show these homeostatic changes? Please provide some examples. The second (non Ricaurte) study seemed quite clear:
'Here we demonstrate that amphetamine treatment, similar to that used clinically for adult ADHD, damages dopaminergic nerve endings in the striatum of adult nonhuman primates.'
How does that show evidence of merely 'plastic changes'?
>>Also, ever since his hysterical MDMA mess-ups (where it was later found that they accidently used methamphetamine instead of MDMA, later being long after MDMA's neurotoxicity was trumpeted all over the news media) I don't really trust anything coming out of Ricaurte's lab.>>Other than that study, neurotoxicity from dextroamphetamine (unlike dextromethamphetamine, which has an additional mechanism of neurotoxicity that has a good chance of being active at therapeutic dosing, due to its serotonergic affinity) neurotoxicity is not known to occur at anything near human therapeutic doses of amphetamine.
Please cite evidence. From 'Update on amphetamine neurotoxicity and its relevance to the treatment of ADHD.':
'In early studies, high doses of amphetamine, comparable to amounts used by addicts, were shown to damage dopaminergic pathways. More recent studies, using therapeutic regimens, appear contradictory. One paradigm shows significant decreases in striatal dopamine and transporter density after oral administration of "therapeutic" doses in primates. Another shows morphological evidence of "trophic" dendritic growth in the brains of adult and juvenile rats given systemic injections mimicking "therapeutic" treatment. Imaging studies of ADHD-diagnosed individuals show an increase in striatal dopamine transporter availability that may be reduced by methylphenidate treatment.'
Finally in respect to the previous post about hyperthermia being a contributing factor in d-amphetamine and l-ephedrine induced neurotoxicity - From 'An Evalutaion of l-Ephedrine Neurotoxicity with respect to Hyperthermia and Caudate/Putamen Microdialysate Levels of Ephedrine, Dopamine, Serotonin, and Glutamate':
Although the 3 x 40 mg/kg dose of l-ephedrine should produce CPu extracellular dopamine levels more comparable to the 4 x 5 mg/kg d-amphetamine dose, the excessive cooling necessary to prevent lethality would obtund dopamine and 5-HT levels. The reduction in dopamine and 5-HT levels is not the only mechanism by which cooling would reduce long-term dopamine depletions. We have previously observed that animals dosed with 4 x 10 mg/kg d-amphetamine in a cold environment have higher CPu microdialysate dopamine levels than animals dosed with 4 x 5 mg/kg d-amphetamine at 23°C temperature but no significant long-term dopamine depletions (Bowyer et al., 1993Go). The cooling should also reduce oxidative stress, since indices of oxidative stress produced by quinones of dopamine are decreased when hyperthermia does not occur during methamphetamine exposure (LaVoie and Hastings, 1999Go). Increased oxidative stress and reactive oxidative species of dopamine, such as 6-hydroxy-dopamine and quinones of dopamine, have been postulated to be mediators of dopamine neurotoxicity in the CPu (Graham, 1978Go; O'Dell et al., 1991Go; Seiden and Sabol, 1995Go; Stokes et al., 1999Go; Yamamoto and Zhu, 1998Go). Thus, from these previous studies, it seems likely that the greater the dopamine release and hyperthermia the greater the generation of reactive dopamine-like species. However, it is possible that the increase of dopamine within the dopaminergic terminals of the CPu is primarily mediating long-term neurotoxicity (LaVoie and Hastings, 1999Go).
http://toxsci.oxfordjournals.org/cgi/content/full/55/1/133
In regards to preventing brain damage (besides the use of memantine) here is one study I found using neuroprotective agents to prevent monoamine depletion after methamphetamine:
Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1908047>
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poster:West
thread:845093
URL: http://www.dr-bob.org/babble/20080814/msgs/846392.html